ROCHESTER, Minn., July 2, 2007-Women with at least three sites of
cellular atypia in breast tissue are nearly eight times more likely
than average women to develop breast cancer, according to findings
of a Mayo Clinic Cancer Center led study of women with atypical
hyperplasia. The findings are published in the July 1 issue of the
Journal of Clinical Oncology.

Several previous studies have shown that atypical hyperplasia
(also called atypia) in breast tissue is a major risk factor for
breast cancer. Women who have a breast biopsy and are diagnosed
with atypia are considered at high risk. Many are counseled to
consider preventive medications such as tamoxifen or other
risk-reducing approaches. However, questions remained from prior
research on whether a positive family history further increases
risk in women with atypia and for how long the increased risk in
women with atypia lasts.

"The most commonly used tool for risk prediction in women with
atypia is the Gail model, which may predict inaccurately because
our study shows that family history does not change risk
significantly in women with atypia," says Amy Degnim, M.D., a Mayo
Clinic surgeon and study author. "Our findings indicate that women
with atypia have a higher absolute risk for breast cancer than
previously estimated. This risk is 25 percent over 25 years and is
much higher in women with multiple areas of atypia and
calcification." The Gail model predicts risk by using age at onset
of menses, age at birth of first child, number of previous breast
biopsies, presence of atypia, and number of close relatives with
breast cancer.

While the Mayo Clinic study found that family history did not
further increase risk, age at diagnosis of atypia did affect risk,
with younger women (under age 45) more than twice as likely to
develop breast cancer compared to women diagnosed with atypia after
55. The number of areas of atypical hyperplasia was significant as
well. With one area of atypia, breast cancer risk was 2.3-fold
compared to the general population; this risk more than doubled
when two sites were found and increased to nearly eightfold as
sites increased to three or more. The group of women with the
highest risk had three or more areas of atypia and calcification --
with a 10.4-fold risk over the general population.

"With the ability to stratify the risk of breast cancer in women
with atypia, we can have more informed discussions with our
patients regarding their personal risk," says Dr. Degnim. "This
will help us to have individualized discussions regarding how
aggressively to pursue risk-reduction treatments."

These findings resulted from reviewing the records of 331 women
with atypia identified within the Mayo cohort of 9,376 women who
had benign breast biopsies surgically obtained between 1967 and
1991. More than half (55.9 percent) of the women were over age 55
when diagnosed with atypia, and 42.9 percent had a family history
of breast cancer. The majority (68.6 percent) of women showed
calcification in the biopsy tissue, and 40 percent had multiple
sites of atypical hyperplasia.

The American Cancer Society reports that more than 240,000 women
will be diagnosed in the United States this year with breast
cancer, and more than 40,000 will die from it. Dr. Degnim and her
fellow researchers have been working to better understand the steps
that precede breast cancer and which of them can be recognized in
benign breast tissue. The current study contributes to Mayo's
emerging model that seeks to define every woman's risk more
precisely and to tailor screening and risk-reduction measures to
women depending on their individual risks.